38 research outputs found

    Characterization of human cytomegalovirus genome diversity in immunocompromised hosts by whole genomic sequencing directly from clinical specimens

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    Background: Advances in next-generation sequencing (NGS) technologies allow comprehensive studies of genetic diversity over the entire genome of human cytomegalovirus (HCMV), a significant pathogen for immunocompromised individuals. Methods: NGS was performed on target-enriched sequence libraries prepared directly from a variety of clinical specimens (blood, urine, breast-milk, respiratory samples, biopsies and vitreous humor) obtained longitudinally or from different anatomical compartments from 20 HCMV-infected patients (renal transplant recipients, stem cell transplant recipients and congenitally infected children). Results: De novo assembled HCMV genome sequences were obtained for 57/68 sequenced samples. Analysis of longitudinal or compartmental HCMV diversity revealed various patterns: no major differences were detected among longitudinal, intra-individual blood samples from 9/15 patients and in most of the patients with compartmental samples, whereas a switch of the major HCMV population was observed in six individuals with sequential blood samples and upon compartmental analysis of one patient with HCMV retinitis. Variant analysis revealed additional aspects of minor virus population dynamics and antiviral resistance mutations. Conclusions: In immunosuppressed patients, HCMV can remain relatively stable or undergo drastic genomic changes that are suggestive of the emergence of minor resident strains or de novo infection

    Evaluation of Indirect Fluorescent Antibody Assays Compared to Rapid Influenza Diagnostic Tests for the Detection of Pandemic Influenza A (H1N1) pdm09

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    Performance of indirect fluorescent antibody (IFA) assays and rapid influenza diagnostic tests (RIDT) during the 2009 H1N1 pandemic was evaluated, along with the relative effects of age and illness severity on test accuracy. Clinicians and laboratories submitted specimens on patients with respiratory illness to public health from April to mid October 2009 for polymerase chain reaction (PCR) testing as part of pandemic H1N1 surveillance efforts in Orange County, CA; IFA and RIDT were performed in clinical settings. Sensitivity and specificity for detection of the 2009 pandemic H1N1 strain, now officially named influenza A(H1N1)pdm09, were calculated for 638 specimens. Overall, approximately 30% of IFA tests and RIDTs tested by PCR were falsely negative (sensitivity 71% and 69%, respectively). Sensitivity of RIDT ranged from 45% to 84% depending on severity and age of patients. In hospitalized children, sensitivity of IFA (75%) was similar to RIDT (84%). Specificity of tests performed on hospitalized children was 94% for IFA and 80% for RIDT. Overall sensitivity of RIDT in this study was comparable to previously published studies on pandemic H1N1 influenza and sensitivity of IFA was similar to what has been reported in children for seasonal influenza. Both diagnostic tests produced a high number of false negatives and should not be used to rule out influenza infection

    Distinguishing Characteristics between Pandemic 2009–2010 Influenza A (H1N1) and Other Viruses in Patients Hospitalized with Respiratory Illness

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    BACKGROUND: Differences in clinical presentation and outcomes among patients infected with pandemic 2009 influenza A H1N1 (pH1N1) compared to other respiratory viruses have not been fully elucidated. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective study was performed of all hospitalized patients at the peak of the pH1N1 season in whom a single respiratory virus was detected by a molecular assay targeting 18 viruses/subtypes (RVP, Luminex xTAG). Fifty-two percent (615/1192) of patients from October, 2009 to December, 2009 had a single respiratory virus (291 pH1N1; 207 rhinovirus; 45 RSV A/B; 37 parainfluenza; 27 adenovirus; 6 coronavirus; and 2 metapneumovirus). No seasonal influenza A or B was detected. Individuals with pH1N1, compared to other viruses, were more likely to present with fever (92% & 70%), cough (92% & 86%), sore throat (32% & 16%), nausea (31% & 8%), vomiting (39% & 30%), abdominal pain (14% & 7%), and a lower white blood count (8,500/L & 13,600/L, all p-values<0.05). In patients with cough and gastrointestinal complaints, the presence of subjective fever/chills independently raised the likelihood of pH1N1 (OR 10). Fifty-five percent (336/615) of our cohort received antibacterial agents, 63% (385/615) received oseltamivir, and 41% (252/615) received steroids. The mortality rate of our cohort was 1% (7/615) and was higher in individuals with pH1N1 compared to other viruses (2.1% & 0.3%, respectively; p = 0.04). CONCLUSIONS/SIGNIFICANCE: During the peak pandemic 2009-2010 influenza season in Rhode Island, nearly half of patients admitted with influenza-like symptoms had respiratory viruses other than influenza A. A high proportion of patients were treated with antibiotics and pH1N1 infection had higher mortality compared to other respiratory viruses

    Guillain–Barré syndrome associated with autochthonous infection by hepatitis E virus subgenotype 3c

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    In this report, we present a case of a 50-year-old immunocompetent man with Guillain–Barré syndrome (GBS) associated with an autochthonous hepatitis E virus (HEV) infection. The patient presented with tetraparesis and elevated liver enzymes. HEV infection was confirmed serologically and by polymerase chain reaction (PCR) from blood and stool. Phylogenetic analysis revealed a novel HEV genotype 3 isolate closely related to other subgenotype 3c isolates from pig livers purchased in Germany. This indicates an autochthonous, potentially food-related hepatitis E and is, to our knowledge, the first report about a neurological syndrome associated with an HEV subgenotype 3c infection

    Ein Influenza und Respiratory Syncytial Virus Screening-Programm zur Detektion asymptomatisch infizierter hämatologisch-onkologischer Patienten

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    Introduction: Respiratory syncytial virus (RSV) and influenza virus infections are a significant healthcare risk for immunocompromised patients. In addition to community onset, nosocomial acquisition and transmission may also occur. Detection of asymptomatic shedders (e.g., patients in the incubation period or immunosuppressed long term shedders) facilitates control of nosocomial transmission.Methods: To strengthen the existing infection control concept, a PCR-based screening for RSV and influenza virus was implemented for all patients lacking respiratory symptoms (asymptomatic patients) who were hospitalized on an adult and a pediatric hemato-oncological ward. Laboratory results of this screening were analyzed retrospectively.Results: 665 respiratory specimens were obtained for screening from 251 patients (26% were 18 years and younger) from December 2016 to April 2017. In 23 patients without respiratory symptoms, either influenza virus or RSV infection was found, resulting in a detection rate of about 9%. In 6 patients, the infection was presumably detected during the incubation period, because an increase of viral load was observed in subsequent specimens. Positive screening results facilitated timely implementation of adequate infection control precautions. Nosocomial clusters of RSV or influenza were not detected during the screening period on the two wards.Conclusion: The seasonal screening program expanded our existing infection control concept in terms of patients lacking respiratory symptoms who shed influenza virus or RSV. It enabled us to identify 23 RSV or influenza infections in patients lacking respiratory symptoms in a 4-month period and thus to rapidly take isolation precautions.Einleitung: Infektionen mit dem Respiratory Syncytial Virus (RSV) und dem Influenzavirus stellen für immunsupprimierte Patienten ein relevantes Gesundheitsrisiko dar. Die Infektion mit diesen Viren erfolgt häufig außerhalb des Krankenhauses, jedoch sind auch ein nosokomialer Erwerb und nosokomiale Übertragungen möglich. Die rechtzeitige Detektion von asymptomatischen Virusausscheidern (z.B. Patienten in der Inkubationsphase oder asymptomatische Langzeitausscheider bei Immunsuppression) kann dazu beitragen, die nosokomiale Verbreitung dieser Erreger zu verhindern.Methoden: Es wurde ein PCR-basiertes Screening-Programm für RSV und Influenza für alle Patienten ohne Symptome einer respiratorischen Erkrankung (asymptomatische Patienten) etabliert, die auf einer pädiatrischen hämatologisch-onkologischen und einer hämatologisch-onkologischen Station für Erwachsene behandelt wurden. Die Ergebnisse dieses Screening-Programms wurden retrospektiv analysiert. Ergebnisse: Von Dezember 2016 bis April 2017 wurden insgesamt 665 respiratorische Proben von 251 asymptomatischen Patienten (davon waren 26% pädiatrische Patienten) gewonnen. Bei 23 dieser Patienten konnte entweder eine RSV- oder eine Influenzainfektion nachgewiesen werden, was einer Detektionsrate von etwa 9% entspricht. 6 der Patienten, die eine ansteigende Viruslast im Verlauf aufwiesen, befanden sich beim Screening mutmaßlich in der Inkubationsphase. Positive Screening-Ergebnisse führten zur Implementierung zusätzlicher Hygienemaßnahmen (z.B. Isolation, Barrierepflege). Influenza und/oder RSV Häufungen wurden auf den beiden Stationen im Screening-Zeitraum nicht detektiert. Schlussfolgerung: Das saisonale Screeningprogramm hat unser bestehendes Hygienekonzept in der Hämatologie und Onkologie in Hinblick auf asymptomatische Virusausscheider erweitert. Es ermöglichte in einer etwa viermonatigen Periode insgesamt 23 asymptomatisch infizierte Patienten zu detektieren und für diese adäquate Hygienemaßnahmen zu ergreifen

    Outcome of pregnancies with recent primary cytomegalovirus infection in first trimester treated with hyperimmunoglobulin: observational study

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    Objective To examine the efficacy of hyperimmunoglobulin (HIG) treatment in women with a recent primary cytomegalovirus (CMV) infection up to 14weeks' gestation. Methods This is an ongoing observational study conducted at the prenatal medicine departments of the University Hospitals of Tubingen, Bonn, Cologne and Erlangen, Germany, as well as at the Laboratory Prof. Gisela Enders and Colleagues in Stuttgart, Germany and the Institute for Medical Virology at the University of Tubingen, Tubingen, Germany. Enrolment criteria were the presence of confirmed recent primary CMV infection in the first trimester and a gestational age at first HIG administration of <= 14 weeks. The following inclusion criteria indicated a recent primary infection: low anti-immunoglobulin (Ig)-G levels, low anti-CMV-IgG avidity in the presence of a positive CMV-IgM test and no positive reactivity or just sero-conversion anti-gB2-IgG-reactivity. HIG administration was started as soon as possible within a few days after the first visit. HIG was administered intravenously at a dose of 200 IU/kg maternal body weight and repeated every 2 weeks until about 18 weeks' gestation. The primary outcome was maternal-fetal transmission at the time of amniocentesis. Multivariate logistic regression analysis was used to determine significant covariates that could predict maternal-fetal transmission. Results We included 149 pregnancies (153 fetuses) that completed the treatment. Median maternal age and weight were 32.0 years and 65.0 kg, respectively. Median gestational age at the time of first referral to one of the four centers was 9.4weeks. Median anti-CMV-IgG level, anti-CMV-IgM index and CMV-IgG avidity were 5.7U/mL, 2.5 and 22.3%, respectively. HIG treatment was started at a median gestational age of 10.6weeks and ended at a median of 17.9weeks. Within this time frame, HIG was administered on average four times in each patient. Amniocentesis was carried out at a median gestational age of 20.4weeks. In 143 (93.5%) of the 153 cases, the fetus was not infected. Maternal- fetal transmission occurred in 10 cases (6.5% (95% CI, 3.2- 11.7%)). On uni- and multivariate logistic regression analysis, the level of anti-IgM index was the only factor associated significantly with maternal- fetal transmission at amniocentesis. However, only four (40.0%) of the 10 cases with maternal- fetal transmission had an anti-IgM index above 11.4, which corresponds to the 95th centile of pregnancies without transmission. Conclusions HIG is a treatment option to prevent maternal- fetal transmission in pregnancy with a primary CMV infection. However, HIG treatment seems to be beneficial primarily in women with a recent primary infection in the first trimester or during the periconceptional period, and when it is administered at a biweekly dose of 200 IU/kg. (C) 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology

    rapidSTRIPE H1N1 Test for Detection of the Pandemic Swine Origin Influenza A (H1N1) Virusâ–ż

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    The rapidSTRIPE H1N1 test, based on a nucleic acid lateral-flow assay, has been developed for diagnosis of a swine-origin influenza A (H1N1) virus. This test is simple and cost-effective and allows specific detection of the S-OIV A (H1N1) virus from swab sampling to final detection on a lateral-flow stripe within 2 to 3 h

    Case report: Immunovirotherapy as a novel add-on treatment in a patient with thoracic NUT carcinoma

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    NUT carcinoma (NC) is a rare and extremely aggressive form of cancer, usually presenting with intrathoracic or neck manifestations in adolescents and young adults. With no established standard therapy regimen and a median overall survival of only 6.5 months, there is a huge need for innovative treatment options. As NC is genetically driven by a single aberrant fusion oncoprotein, it is generally characterized by a low tumor mutational burden, thus making it immunologically cold and insusceptible to conventional immunotherapy. Recently, we have demonstrated that oncolytic viruses (OVs) are able to specifically infect and lyse NC cells, thereby turning an immunologically cold tumor microenvironment into a hot one. Here, we report an intensive multimodal treatment approach employing for the first time an OV (talimogene laherparepvec (T-VEC); IMLYGIC (R)) together with the immune checkpoint inhibitor pembrolizumab as an add-on to a basic NC therapy (cytostatic chemotherapy, radiation therapy, epigenetic therapy) in a patient suffering from a large thoracic NC tumor which exhibits an aberrant, unique BRD3:NUTM1 fusion. This case demonstrates for the first time the feasibility of this innovative add-on immunovirotherapy regimen with a profound, repetitive and durable replication of T-VEC that is instrumental in achieving tumor stabilization and improvement in the patient's quality of life. Further, a previously unknown BRD3:NUTM1 fusion gene was discovered that lacks the extraterminal domain of BRD3
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